Adjuvant RT or CRT is typically delivered after RH for early-stage cervical cancer patients with certain risk factors. One study from Levine Cancer Institute (one of the LACC trial centers) indicated that adjuvant therapy might be an important confounder for the survival outcomes of MIS and open surgery [11]. MIS is associated with a shorter recovery time and a lower risk of postoperative complications than ORH [5], and the TI from surgery to adjuvant may differ. We hypothesized that the initiation of postoperative RT or CRT might impact survival outcomes among the treatment-related variables. The results of the present study have confirmed the hypothesis.
We found that the DFS and OS had no significant difference in both groups, despite the TI from surgery to postoperative CT or RT being shorter in the MIS group. Tumor size > 4 cm and TI from surgery to RT beyond seven weeks were revealed to be independent predictive variables for DFS after being adjusted for important prognostic parameters.
The study results showed that the DFS and OS were similar between the MIS and ORH groups, which were different from the outcomes of the LACC trial. The following factors might explain the different results. Firstly, the surgical-related factors that may result in poor survival, such as utilizing uterine manipulator, the effect of insufflation gas (CO2), and the degree of resection, can be improved by postoperative RT or CRT [5, 6, 8, 16]. Furthermore, the TI from surgery to postoperative CT and RT were shorter in the MIS group, resulting in a shorter overall treatment time, which was a critical factor for pelvic control and survival in cervical cancer[17].
Most patients in the study received pelvic IMRT, which could reduce the toxicity of postoperative RT with a non-inferior survival outcome[18, 19]. The update of GOG 92[9], a randomized trial of postoperative RT versus no further therapy in stage IB cervical cancer after RH, revealed that the 3-year PFS and OS was around 86% and 88% for patients with intermediate-risk factors. In high-risk patients, the three-year PFS and OS were around 84% and 88% [7]. Similarly, our research indicated that the 3-year DFS rates and OS rates in ORH and MIS groups were 89.7% vs. 85.2% and 98.5% vs. 89.9%, respectively. Meanwhile, IMRT helps decrease GI and GU toxicity, with a greater incidence of grade 3 or higher acute HT complications[20].
Tumor size is generally accepted as an independent prognostic factor [21, 22]. However, the optimal time to start postoperative RT in individuals with risk factors has not been well defined. The role of postoperative adjuvant therapy is to control the residual subclinical disease. Some animal studies revealed that surgery might stimulate angiogenesis by releasing circulating growth factors and accelerating the growth of minimal residual disease[23, 24]. The delay in postoperative adjuvant therapy could allow more time for a tumor cell to proliferate, and the early initiation of postoperative adjuvant treatment might improve oncological outcomes. In the present study, the median time for patients to receive postoperative adjuvant CT and RT were seven days vs. eight days, and 28 days vs. 35 days in MIS and ORH groups, respectively. We delivered adjuvant therapy in such a short TI and got a favorable survival outcome. It showed that patients received postoperative adjuvant treatment timely is very important to ensure the treatment outcome.
We found that the median TI from surgery to RT beyond seven weeks had an independent significant adverse effect on survival. The median TI from surgery to RT was within seven weeks; despite some differences in both groups, the slight disparity has little impact on DFS. Consistent with our results, Hanprasertpong J. et al. [25] found that delaying adjuvant therapy in patients with early-stage squamous cell cervical cancer beyond four weeks after surgery resulted in a lower RFS. And Jhawar. et al. [26] concluded that postoperative therapy should be administered within eight weeks after surgery whenever possible. Although the definite initiate time of postoperative adjuvant therapy is not clear in cervical cancer, it is recommended for postoperative RT to be delivered as early as possible.
This study has some limitations worth noting. It is a retrospective study performed at a single institution, and the retrospective study design has inherent biases and limitations. A multicenter study with larger sample size and longer follow-up duration is needed to verify these results.
In conclusion, for the early-stage (IB1-IIA2) cervical cancer patients with intermediate or high-risk factors who received postoperative RT or CRT, no matter they received ORH or MIS as their primary treatment, the DFS and OS had no significant difference, despite TI from surgery to postoperative adjuvant therapy being shorter in the MIS group than ORH.